P1466: EFFECT OF LUSPATERCEPT ON BONE MINERAL DENSITY IN PATIENTS WITH BETA‑THALASSEMIA ENROLLED IN THE PHASE 3 BELIEVE TRIAL
Authors: Thomas D. Coates, Maria Domenica Cappellini, Sujit Sheth, Kevin H.M. Kuo, Antonio Giulio Piga, Antonis Kattamis, Martina Perin, Frederik Lersch, Jeevan K. Shetty, Yinzhi Lai, Wen-Ling Kuo, Ali T. Taher
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Osteoporosis and osteopenia are common in patients (pts) with β-thalassemia due to bone marrow expansion, chronic anemia, ineffective erythropoiesis, and hormone dysregulation. Reduced bone mineral density (BMD) results in an increased risk of bone fractures. It is therefore crucial that treatments for pts with β-thalassemia do not further worsen BMD. Correction of anemia by transfusion limits bone marrow expansion and may maintain or improve BMD in pts with thalassemia. Luspatercept is an erythroid maturation agent approved in the EU and USA to treat anemia in adult pts with β-thalassemia who require red blood cell (RBC) transfusions. Results from the phase 3, double-blind, randomized, placebo-controlled, multicenter BELIEVE trial (NCT02604433) showed that luspatercept significantly reduced RBC transfusion burden in the first 48 wk of treatment (Cappellini MD, N Engl J Med 2020;382;1219–31), and subsequent analysis has demonstrated durable efficacy (Cappellini MD, HemaSphere 2022;6 [Suppl 3]. Abstract 270). However, the impact of luspatercept on BMD has yet to be assessed. Aims: To evaluate the effect of long-term luspatercept treatment on BMD in pts enrolled in the BELIEVE trial. Methods: Enrolled pts were adults with β-thalassemia or hemoglobin E/β-thalassemia who required RBC transfusions (6–20 RBC units/24 wk prior to randomization, no transfusion-free period >35 days). Pts were randomized 2:1 to receive luspatercept (1.0–1.25 mg/kg) or placebo subcutaneously every 3 wk. BMD of total hip and lumbar spine were assessed using dual-energy X-ray absorptiometry (DXA) and T-scores calculated at baseline and every 48 wk. Data for placebo pts are presented at baseline and wk 48 as most pts had discontinued placebo treatment by wk 96. After study unblinding, data were assessed only for pts who were randomized to luspatercept. Change from baseline was calculated using an ANCOVA model with the geographical region at randomization and baseline measurements as covariates. Results: The BELIEVE trial followed 336 pts from May 2016 to January 2021; 224 pts were randomized to receive luspatercept and 112 to placebo. BMD in the luspatercept arm up to wk 96 remained similar to baseline for hip (mean [standard deviation (SD)] change +0.02 [0.064] g/cm2) and spine (mean [SD] change +0.01 [0.065] g/cm2). BMD for hip and spine were comparable between luspatercept and placebo arms at wk 48 (Figure). Hip T-scores in the luspatercept arm were slightly improved from baseline to wk 96 (mean [SD] change +0.15 [0.437]), whereas spine T-scores remained similar to baseline (Figure). The mean changes from baseline were not significantly different between luspatercept and placebo for any measure at wk 48 (hip BMD least squares mean of difference [95% CI] 0.00 [−0.01 to 0.01], P=0.9201; hip T-score −0.02 [−0.12 to 0.08], P=0.6912; spine BMD −0.01 [−0.02 to 0.01], P=0.4620; spine T-score −0.10 [−0.25 to 0.04]; P=0.1475). BMD remained similar to baseline up to wk 192 of luspatercept treatment (hip mean [SD] change +0.01 [0.080] g/cm2; spine mean [SD] change −0.00 [0.053] g/cm2), as did T-scores (hip mean [SD] change +0.09 [0.537]; spine mean [SD] change +0.19 [0.714]). Summary/Conclusion: After 48 wk of treatment, BMD and T-scores of the hip and lumbar spine were similar to baseline and similar between the luspatercept and placebo arms in pts with β-thalassemia from the BELIEVE trial. With longer-term luspatercept treatment up to wk 192, BMD remained near baseline levels, indicating that patient bone health remained stable with luspatercept treatment. Importantly, BMD did not significantly worsen despite reduced transfusion burden.Keywords: Clinical trial, Thalassemia, Bone mineral density